Human Milk FortificationNCT06870318
Enrichment of Human Milk With Human and Bovine Milk-based Fortifiers for Very Preterm Infants: a Meta-analysis
An observational study of Human Milk Fortification and Very Low Birth Weight Baby, run by The Hospital for Sick Children at 2 sites in 2 countries.
Trial summary
Research has shown that provision of mother's milk is the optimal way to feed very low birthweight (VLBW) infants. Many infants will require a supplement to mother's milk, pasteurized donor human milk (PDHM) compared to preterm formula is the most appropriate supplement as it has been shown to reduce the risk of… Read more about this study
- Who is it for?
- Ages 1 hour to 21 days
- Conditions the study is for
- Human Milk Fortification, Very Low Birth Weight Baby, Human Milk Nutrition
- How many people
- 355 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Oct 2014to 1 Sep 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 hour to 21 days
- All sexes
- No healthy volunteers
- Child
Study population: Participants of the OptiMoM and N-Forte trial are VLBW infants fed exclusively Human Milk.
Who may be able to join
- Infant is a participant of the OptiMoM or the N-Forte trial.
Who cannot join
None listed.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Nutrient Enrichment of Human Milk With Human and Bovine Milk-based Fortifiers for Very Preterm Infants: an Individual Participant Data Meta-analysis
Research has shown that provision of mother's milk is the optimal way to feed very low birthweight (VLBW) infants. Many infants will require a supplement to mother's milk, pasteurized donor human milk (PDHM) compared to preterm formula is the most appropriate supplement as it has been shown to reduce the risk of necrotizing enterocolitis (NEC).
Most available evidence suggests neither mother's milk nor PDHM will meet the elevated nutritional requirements of VLBW infants without multi-nutrient fortification. Globally, the current standard of care is to use bovine protein-based nutrient fortifiers to meet these elevated nutrient requirements. Given the known benefits of mother's milk, the reduction in the risk of NEC with use of PDHM as a supplement, and the availability of human milk-based multi-nutrient fortifiers (HMBF), there has been considerable interest in the efficacy of HMBF over the less costly bovine milk-based fortifiers (BMBF).
Read more
This study is an analysis of individual participant data merged from randomized control trials that examined the efficacy of HMBF compared to BMBF during hospitalization, on the risk of death and severe morbidity or major feeding interruption. Participants of the trials included in the analyses were fed exclusively with human milk or a supplement of pasteurized donor human milk (PDHM).
Only two RCTs met this criteria -OptiMoM and the N-forte trial. In both studies the intervention aligned to commence upon randomization into the HMBF or BMBF groups. The difference between the OptiMoM and N-forte feeding protocols was that the later allowed for individualized fortification based on milk analysis whereas OptiMoM used standard fortification, predominant in Canada and globally.
For OptiMoM, the feeding intervention continued until infants were 84 days of age, discharge, or when the infant consumed ≥2 complete oral feeds daily. For N-forte trial, the feeding intervention ended when babies reached 34 weeks (zero days). Both studies followed participants and continued data collection if transferred to a level II NICU for convalescence (OptiMoM) or home care service followed closely by NICU nurses (N-forte) until discharge.
- Conditions
- Human Milk Fortification, Very Low Birth Weight Baby, Human Milk Nutrition, Human Milk Feeding, Necrotizing Enterocolitis (NEC), Late Onset Neonatal Sepsis
- Being tested
- No intervention; Observational study
- Keywords
- Bovine based vs human milk based fortifiers, RCTs meta-analysis, Human Milk Fortifiers (HMF)
- Medical subject headings
- Enterocolitis, Necrotizing, Neonatal Sepsis, Infant Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No intervention; Observational studyOther
OptiMoM-NForte is meta-analysis study (observational secondary use of data), the investigators will analyze data from the OptiMoM and NForte trials. No interventions form part of this study.
| Study group | Role | What they receive |
|---|---|---|
| Human milk-based multi-nutrient fortifiers (HMBF) group | Infants born VLBW fed exclusively with Human Milk (parent milk or pasteurized donor milk) fortified with HMBF Receives: Other: No intervention; Observational study | |
| Bovine milk-based fortifiers (BMBF) group | Infants born VLBW fed exclusively with Human Milk (parent milk or pasteurized donor milk) fortified with BMBF Receives: Other: No intervention; Observational study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with composite of NEC (NEC II-III), culture-proven late-onset sepsis and mortality.
The first primary outcome is a binary (yes/no) composite of NEC (NEC II-III), culture-proven late-onset sepsis and mortality.
Measured: From study day 1 through hospitalization, approximately 60 days.
Percentage of infants with an interruption in enteral feeding.
The second primary outcome is the percentage of infants with an interruption in enteral feeding after commencement of the intervention (e.g. Study Day 1), unrelated to a clinical procedure, that lasted for ≥12 h or a >50% reduction in volume over the same time-frame.
Measured: Through feeding intervention, approximately 50 days.
Secondary outcomes (6)
Days from birth to full enteral feeding.
Full enteral feeding (defined as 150 ml/kg/d).
Measured: Approximately 10 days.
Number of participants with NEC II-III.
NEC II-III defined using Bell's staging criteria with Bell Stage >II classification consisting of clinical symptoms and evidence of septic shock, pneumatosis, bowel perforation, or histologic evidence of bowel ischemia consistent with NEC on bowel resection.
Measured: From study day 1 through hospitalization, approximately 60 days.
Number of participants with late onset-sepsis.
Late-onset sepsis was defined as clinical symptoms and a positive culture in blood, cerebrospinal fluid, or suprapubic or catheter urine ≥5 days post-partum.
Measured: From study day 1 through hospitalization, approximately 60 days.
Total deaths prior to discharge.
Total deaths prior to hospital discharge or discharge from home-care in Sweden.
Measured: From study day 1 through hospitalization, approximately 60 days.
Number of participants with bronchopulmonary dysplasia.
Bronchopulmonary dysplasia defined as a need for oxygen support at 36 weeks 0 days.
Measured: Assessed at 36 weeks 0 days post-conceptional age.
Number of participants with severe retinopathy of prematurity (ROP).
Severe retinopathy of prematurity (ROP) that was treated (e.g. laser or intraocular antivascular injection).
Measured: From study day 1 through hospitalization, approximately 60 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2025
- Study start1 Oct 2014
- Primary completion1 Sep 2022
- Study completion1 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Human Milk FortificationStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Retrospective
- Enrolment
- 355 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Umeå University, Region Östergötland
- Responsible party
- Principal investigator, Deborah O'Connor, The Hospital for Sick Children
- Investigators
- Deborah L O'Connor, PhD, RN, Principal investigator, The Hospital for Sick ChildrenMagnus Domellöf, MD, PhD, Principal investigator, Umeå University, Umeå (UMU)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06870318
- Sponsor's protocol ID
- 4784
- Status last verified
- Mar 2025
- First submitted
- 3 Feb 2025
- Last updated
- 11 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data transfer will take place via Secure File Transfer Protocol (SFTP). A sub-agreement which covers data sharing and confidentiality is in place.
Publications
Jensen GB, Ahlsson F, Domellof M, Elfvin A, Naver L, Abrahamsson T. Nordic study on human milk fortification in extremely preterm infants: a randomised controlled trial-the N-forte trial. BMJ Open. 2021 Nov 23;11(11):e053400. doi: 10.1136/bmjopen-2021-053400.
PubMed 34815288Corrigendum for O'Connor et al. Nutrient enrichment of human milk with human and bovine milk-based fortifiers for infants born weighing < 1250 g: a randomized clinical trial. Am J Clin Nutr 2018;108:108-16. Am J Clin Nutr. 2020 May 1;111(5):1112. doi: 10.1093/ajcn/nqaa042. No abstract available.
PubMed 32367115
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nutrient Enrichment of Human Milk With Human and Bovine Milk-based Fortifiers for Very Preterm Infants: an Individual Participant Data Meta-analysis
- ClinicalTrials.gov ID
- NCT06870318
- Acronym / sponsor ID
- 4784
- Conditions
- Human Milk Fortification, Very Low Birth Weight Baby, Human Milk Nutrition, Human Milk Feeding, Necrotizing Enterocolitis (NEC), Late Onset Neonatal Sepsis
- Keywords
- Bovine based vs human milk based fortifiers, RCTs meta-analysis, Human Milk Fortifiers (HMF)
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 355 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Umeå University, Region Östergötland
- Study start
- 1 Oct 2014 (actual)
- Primary completion
- 1 Sep 2022 (actual)
- Study completion
- 1 Sep 2022 (actual)
- First posted
- 11 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Research has shown that provision of mother's milk is the optimal way to feed very low birthweight (VLBW) infants. Many infants will require a supplement to mother's milk, pasteurized donor human milk (PDHM) compared to preterm formula is the most appropriate supplement as it has been shown to reduce the risk of necrotizing enterocolitis (NEC).
Most available evidence suggests neither mother's milk nor PDHM will meet the elevated nutritional requirements of VLBW infants without multi-nutrient fortification. Globally, the current standard of care is to use bovine protein-based nutrient fortifiers to meet these elevated nutrient requirements. Given the known benefits of mother's milk, the reduction in the risk of NEC with use of PDHM as a supplement, and the availability of human milk-based multi-nutrient fortifiers (HMBF), there has been considerable interest in the efficacy of HMBF over the less costly bovine milk-based fortifiers (BMBF).
This study is an analysis of individual participant data merged from randomized control trials that examined the efficacy of HMBF compared to BMBF during hospitalization, on the risk of death and severe morbidity or major feeding interruption. Participants of the trials included in the analyses were fed exclusively with human milk or a supplement of pasteurized donor human milk (PDHM).
Only two RCTs met this criteria -OptiMoM and the N-forte trial. In both studies the intervention aligned to commence upon randomization into the HMBF or BMBF groups. The difference between the OptiMoM and N-forte feeding protocols was that the later allowed for individualized fortification based on milk analysis whereas OptiMoM used standard fortification, predominant in Canada and globally.
For OptiMoM, the feeding intervention continued until infants were 84 days of age, discharge, or when the infant consumed ≥2 complete oral feeds daily. For N-forte trial, the feeding intervention ended when babies reached 34 weeks (zero days). Both studies followed participants and continued data collection if transferred to a level II NICU for convalescence (OptiMoM) or home care service followed closely by NICU nurses (N-forte) until discharge.
Study design
- Observational model
- Other
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Human milk-based multi-nutrient fortifiers (HMBF) group | – | Other: No intervention; Observational studyInfants born VLBW fed exclusively with Human Milk (parent milk or pasteurized donor milk) fortified with HMBF |
| Bovine milk-based fortifiers (BMBF) group | – | Other: No intervention; Observational studyInfants born VLBW fed exclusively with Human Milk (parent milk or pasteurized donor milk) fortified with BMBF |
Who may qualify
- Ages
- 1 hour to 21 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Participants of the OptiMoM and N-Forte trial are VLBW infants fed exclusively Human Milk.
Key inclusion criteria (1 listed)
- Infant is a participant of the OptiMoM or the N-Forte trial.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No intervention; Observational studyOptiMoM-NForte is meta-analysis study (observational secondary use of data), the investigators will analyze data from the OptiMoM and NForte trials. No interventions form part of this study. | Other | Bovine milk-based fortifiers (BMBF) group, Human milk-based multi-nutrient fortifiers (HMBF) group |
Primary outcome
Number of participants with composite of NEC (NEC II-III), culture-proven late-onset sepsis and mortality.
Time frame: From study day 1 through hospitalization, approximately 60 days.
The first primary outcome is a binary (yes/no) composite of NEC (NEC II-III), culture-proven late-onset sepsis and mortality.
Percentage of infants with an interruption in enteral feeding.
Time frame: Through feeding intervention, approximately 50 days.
The second primary outcome is the percentage of infants with an interruption in enteral feeding after commencement of the intervention (e.g. Study Day 1), unrelated to a clinical procedure, that lasted for ≥12 h or a >50% reduction in volume over the same time-frame.
6 secondary outcomes
Days from birth to full enteral feeding.
Time frame: Approximately 10 days.
Number of participants with NEC II-III.
Time frame: From study day 1 through hospitalization, approximately 60 days.
Number of participants with late onset-sepsis.
Time frame: From study day 1 through hospitalization, approximately 60 days.
Total deaths prior to discharge.
Time frame: From study day 1 through hospitalization, approximately 60 days.
Number of participants with bronchopulmonary dysplasia.
Time frame: Assessed at 36 weeks 0 days post-conceptional age.
Number of participants with severe retinopathy of prematurity (ROP).
Time frame: From study day 1 through hospitalization, approximately 60 days.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2025.
- Results publication: PubMed 34815288Jensen GB, Ahlsson F, Domellof M, Elfvin A, Naver L, Abrahamsson T. Nordic study on human milk fortification in extremely preterm infants: a randomised controlled trial-the N-forte trial. BMJ Open. 2021 Nov 23;11(11):e053400. doi: 10.1136/bmjopen-2021-053400.
- Results publication: PubMed 32367115Corrigendum for O'Connor et al. Nutrient enrichment of human milk with human and bovine milk-based fortifiers for infants born weighing < 1250 g: a randomized clinical trial. Am J Clin Nutr 2018;108:108-16. Am J Clin Nutr. 2020 May 1;111(5):1112. doi: 10.1093/ajcn/nqaa042. No abstract available.
- Individual participant dataSharing planned: Yes. Data transfer will take place via Secure File Transfer Protocol (SFTP). A sub-agreement which covers data sharing and confidentiality is in place.
Related trials for Human Milk Fortification
Active, not recruiting
Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development
Preterm Birth, Breast Milk Expression
Active, not recruiting
Early Human Milk Fortification After Early, Exclusive, Enteral Nutrition in Very Preterm Infants
Prematurity, Light-For-Dates
Active, not recruiting
Individualized Fortification of Human Milk for Infants Born ≤ 1250 g (MaxiMoM-InForM)
Very Low Birth Weight Infant
Recruiting
Targeted Fortification of Donor Breast Milk in Preterm Infants
Prematurity; Extreme, Failure to Thrive in Newborn
Not yet recruiting
Growth and Feeding Tolerance in Premature Infants
Feeding Tolerance, Growth
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deborah L O'Connor, PhD, RN principal investigator
The Hospital for Sick Children
Magnus Domellöf, MD, PhD principal investigator
Umeå University, Umeå (UMU)
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Human Milk Fortification and Very Low Birth Weight Baby, run by The Hospital for Sick Children at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with composite of NEC (NEC II-III), culture-proven late-onset sepsis and mortality. (time frame: From study day 1 through hospitalization, approximately 60 days.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06870318, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2025.